| Methods |
Prospective, multi‐site, randomised, clinical trial. |
| Participants |
Patients over 14 years of age with suspected leptospirosis or scrub typhus as described by acute fever without clear source of infection and able to tolerate oral antibiotic therapy. Among all randomised patients (pre‐diagnosis), this study had the lowest ratio of men:women of approximately 2.5:1, predominantly in the 4th decade of life. Laboratory confirmation by titer or culture was required for inclusion in analysis. 10 patients were identified by culture, 45 by four‐fold rise in convalescent titer and 1 by a single titer of at least 1:400. |
| Interventions |
Oral doxycycline 200mg for 1 dose then 100 mg every 12 h for 7 days, or azithromycin 1 g for 1 dose then 500 mg once daily for 2 days. |
| Outcomes |
The primary outcome for this trial was rate of cure defined by afebrile for 48 hours. |
| Notes |
This trial was designed as a non‐inferiority trial of azithromycin against doxycycline among febrile patients. Data presented here was provided on correspondence with the senior author, Dr. Suputtamongkol, who verified for the authors results among those enrolled patients with laboratory confirmed leptospirosis. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
P. 3260, "Independent, computer‐generated, simple random allocation sequences were prepared for each study hospital by the investigator team in Bangkok." |
| Allocation concealment (selection bias) |
Low risk |
P. 3260, "These were sealed in an opaque envelope and numbered. The investigator in each study hospital assigned study participants to their treatment groups after opening the sealed envelope." |
| Blinding (performance bias and detection bias)
All outcomes |
High risk |
P. 3260, the two intervention options were dosed differently and were not used in conjunction with placebo. |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
P. 3260, confirmation of leptospirosis depended upon analysis of both acute and convalescent sera. 89 of 296 patients who were randomised were not assessed at 1 to 2 weeks following discharge. For 23 of these patients nearer term sera 3 to 5 days following admission was available and used for assessing interval titer. |
| Selective reporting (reporting bias) |
High risk |
Pre‐defined outcome was time to defervescence and whether outcomes in the Types of Outcomes section were completely discerned was not discernible. |
| Other bias |
Unclear risk |
Not discerned. |
